Post-Transplant Bone Disease in Kidney Transplant Recipients: Diagnosis and Management.

Kidney transplantation is the preferred gold standard modality of treatment for kidney failure. Bone disease after kidney transplantation is highly prevalent in patients living with a kidney transplant and is associated with high rates of hip fractures. Fractures are associated with increased healthcare costs, morbidity and mortality. Post-transplant bone disease (PTBD) includes renal osteodystrophy, osteoporosis, osteonecrosis and bone fractures. PTBD is complex as it encompasses pre-existing chronic kidney disease-mineral bone disease and compounding factors after transplantation, including the use of immunosuppression and the development of de novo bone disease. After transplantation, the persistence of secondary and tertiary hyperparathyroidism, renal osteodystrophy, relative vitamin D deficiency and high levels of fibroblast growth factor-23 contribute to post-transplant bone disease. Risk assessment includes identifying both general risk factors and kidney-specific risk factors. Diagnosis is complex as the gold standard bone biopsy with double-tetracycline labelling to diagnose the PTBD subtype is not always readily available. Therefore, alternative diagnostic tools may be used to aid its diagnosis. Both non-pharmacological and pharmacological therapy can be employed to treat PTBD. In this review, we will discuss pathophysiology, risk assessment, diagnosis and management strategies to manage PTBD after kidney transplantation.

Recommended calcium intake in adults and children with chronic kidney disease-a European consensus statement.

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800-1000 mg/day and not exceeding 1500 mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs.

Bone marrow-derived exosomes promote inflammation and osteoclast differentiation in high-turnover renal osteodystrophy.

Introduction: Renal osteodystrophy (ROD) is a type of bone metabolic disorder in patients with chronic kidney disease (CKD). Inflammation is associated with bone loss in ROD. However, its precise mechanism has not yet been elucidated. The present study was conducted to investigate whether exosomes (Exos) in bone marrow (BM) are involved in the pathogenesis of high-turnover ROD.Methods: Bone mass, osteoclast number, and pro-inflammatory cytokines levels of BM supernatant were detected in adenine-induced ROD rats. The effect of Exos derived from BM (BM-Exos) of ROD (ROD-Exos) on inflammatory genes and osteoclast differentiation of BM-derived macrophages (BMMs) were further examined. Then, exosomal miRNA sequencing was performed and an miRNA-mRNA-pathway network was constructed.Results: we found increased osteoclasts and decreased bone mass in ROD rats, as well as inflammatory activation in the BM niche. Furthermore, BMMs from ROD rats displayed overproduction of proinflammatory cytokines and increased osteoclast differentiation, accompanied by nuclear factor κB (NF-κB) signaling activation. Mechanistically, we found that ROD-Exos activates NF-κB signaling to promote the release of proinflammatory cytokines and increase osteoclast differentiation of BMMs. Meanwhile, a total of 24 differentially expressed miRNAs were identified between BM-Exos from ROD and normal control (NC). The miRNA-mRNA-pathway network suggests that rno-miR-9a-5p, rno-miR-133a-3p, rno-miR-30c-5p, rno-miR-206-3p, and rno-miR-17-5p might play pivotal roles in inflammation and osteoclast differentiation. Additionally, we validated that the expression of miR-9a-5p is upregulated in ROD-Exos.Conclusion: The BM niche of ROD alters the miRNA cargo of BM-Exos to promote inflammation and osteoclast differentiation of BMMs, at least partially contributing to the pathogenesis of high-turnover ROD.

Inflammation and gut dysbiosis as drivers of CKD-MBD.

Two decades ago, Kidney Disease: Improving Global Outcomes coined the term chronic kidney disease-mineral and bone disorder (CKD-MBD) to describe the syndrome of biochemical, bone and extra-skeletal calcification abnormalities that occur in patients with CKD. CKD-MBD is a prevalent complication and contributes to the excessively high burden of fractures and cardiovascular disease, loss of quality of life and premature mortality in patients with CKD. Thus far, therapy has focused primarily on phosphate retention, abnormal vitamin D metabolism and parathyroid hormone disturbances, but these strategies have largely proved unsuccessful, thus calling for paradigm-shifting concepts and innovative therapeutic approaches. Interorgan crosstalk is increasingly acknowledged to have an important role in health and disease. Accordingly, mounting evidence suggests a role for both the immune system and the gut microbiome in bone and vascular biology. Gut dysbiosis, compromised gut epithelial barrier and immune cell dysfunction are prominent features of the uraemic milieu. These alterations might contribute to the inflammatory state observed in CKD and could have a central role in the pathogenesis of CKD-MBD. The emerging fields of osteoimmunology and osteomicrobiology add another level of complexity to the pathogenesis of CKD-MBD, but also create novel therapeutic opportunities.

Long-term benefits of switching from oral to intravenous calcimimetics in patients on hemodialysis.

AIM: In this study, we aimed to investigate the long-term benefits of switching from oral to intravenous calcimimetics in patients on hemodialysis. MATERIALS AND METHODS: Patients on maintenance hemodialysis at our institution who switched from oral to intravenous calcimimetics between March 1, 2017 and October 31, 2018 were enrolled. We compared tablet number; chronic kidney disease-mineral and bone disorder (CKD-MBD)-related drug cost; and serum corrected calcium, serum phosphorous, and serum intact parathyroid hormone levels before and 1, 2, and 3 years after switching from oral to intravenous calcimimetics. RESULTS: There were 15 patients (11 males and 4 females; mean age 60.9 ± 9.2 years). The tablet numbers and CKD-MBD-related drug cost before and 3 years after switching to calcimimetics were 12.1 ± 8.1 tablets/day vs. 8.4 ± 5.0 tablets/day (p = 0.0371) and 9,654.5 ± 6,206.8 yen (87.8 ± 56.4 U.S. dollars)/week vs. 7,231.7 ± 3,490.9 yen (65.7 ± 31.7 U.S. dollars)/week (p = 0.0406), respectively. CONCLUSION: Switching from oral to intravenous calcimimetics decreased intact parathyroid hormone levels and reduced the tablet numbers and CKD-MBD-related drug cost for a long period without significant adverse effects.

Overview of renal osteodystrophy in Brazil: a cross-sectional study.

INTRODUCTION: The epidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, nationalmulticenter cohort that includes patients with chronic kidney disease (CKD) undergoing bone biopsy. REBRABO aims to provide clinical information on ROD. The main objective of this subanalysis was to describe the profile of ROD, including clinically relevant associations. METHODS: From Aug/2015 to Dec/2021, 511 patients with CKD who performed bone biopsy were included in the REBRABO platform. Patients with no bone biopsy report (N = 40), GFR > 90 mL/min (N = 28), without asigned consent (N = 24), bone fragments inadequate for diagnosis (N = 23), bone biopsy indicated by a specialty other than nephrology (N = 6), and < 18 years old (N = 4) were excluded. Clinical-demographic data (e.g., age, sex, ethnicity, CKD etiology, dialysis vintage, comorbidities, symptoms, and complications related to ROD), laboratory (e.g., serum levels of total calcium, phosphate, parathormone, alkaline phosphatase, 25-hydroxyvitamin D, and hemoglobin), and ROD (e.g., histological diagnosis) were analyzed. RESULTS: Data from 386 individuals were considered in this subanalysis of REBRABO. Mean age was 52 (42-60) years; 198 (51%) were male; 315 (82%) were on hemodialysis. Osteitis fibrosa (OF) [163 (42%)], adynamic bone disease (ABD) [96 (25%)] and mixed uremic osteodystrophy (MUO) [83 (21%)] were the most frequent diagnosis of ROD in our sample; 203 (54%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation, and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher frequency of symptoms. CONCLUSIONS: A high proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.

Role of nutritional vitamin D in chronic kidney disease-mineral and bone disorder: A narrative review.

Chronic kidney disease-mineral and bone disorder has complex and diverse clinical manifestations, including the simplest abnormalities of calcium, phosphorus and parathyroid hormone detected in blood, abnormalities of bone transformation and mineralization in bone, and calcification of blood vessels or other soft tissues detected on imaging. Patients with CKD-MBD combined low bone mineral density and fragility fractures are referred to as CKD-MBD with low bone mineral density. Vascular calcification refers to ectopic deposition of calcium phosphate in the blood vessel walls and heart valves. The degree of vascular calcification was inversely proportional to bone mineral density. The more severe the degree of vascular calcification, the lower the bone mineral density, and the higher the risk of death, indicating that the bone-vascular axis exists. Activation and alteration of the Wnt signaling pathway are central to the treatment of vascular diseases in uremia. Vitamin D supplementation can prevent secondary hyperparathyroidism, activate osteoblasts, relieve muscle weakness and myalgia, and reduce vascular calcification. Nutritional vitamin D may improve vascular calcification in uremia patients by regulating Wnt signaling pathway.

Parathyroidectomy versus oral cinacalcet on cardiovascular parameters in peritoneal dialysis patients with advanced secondary hyperparathyroidism (PROCEED): a randomized trial.

BACKGROUND: This trial aimed to evaluate oral cinacalcet versus total parathyroidectomy (PTx) with forearm autografting on cardiovascular surrogate outcomes and health-related quality of life (HRQOL) measures in dialysis patients with advanced secondary hyperparathyroidism (SHPT). DESIGN: In this pilot prospective randomized trial conducted in two university-affiliated hospitals, 65 adult peritoneal dialysis patients with advanced SHPT were randomized to receive either oral cinacalcet or PTx. Primary endpoints were changes in left ventricular (LV) mass index by cardiac magnetic resonance imaging and coronary artery calcium scores (CACS) over 12 months. Secondary endpoints included changes in heart valves calcium scores, aortic stiffness, biochemical parameters of chronic kidney disease-mineral bone disease (CKD-MBD) and HRQOL measures over 12 months. RESULTS: Changes in LV mass index, CACS, heart valves calcium score, aortic pulse wave velocity and HRQOL did not differ between groups or within groups, despite significant reductions in plasma calcium, phosphorus and intact parathyroid hormone in both groups. Cinacalcet-treated patients experienced more cardiovascular-related hospitalizations than those who underwent PTx (P = .008) but the difference became insignificant after adjusting for baseline difference in heart failure (P = .43). With the same monitoring frequency, cinacalcet-treated patients had fewer hospitalizations due to hypercalcemia (1.8%) than patients who underwent PTx (16.7%) (P = .005). No significant changes were observed in HRQOL measures in either group. CONCLUSIONS: Both cinacalcet and PTx effectively improved various biochemical abnormalities of CKD-MBD and stabilized but did not reduce LV mass, coronary artery and heart valves calcification, or arterial stiffness, or improve patient-centered HRQOL measures in PD patients with advanced SHPT. Cinacalcet may be used in place of PTx for treating advanced SHPT. Long-term and powered studies are required to evaluate PTx versus cinacalcet on hard cardiovascular outcomes in dialysis patients. Trial registration: ClinicalTrials.gov identifier: NCT01447368.

The WNT/ß-catenin system in chronic kidney disease-mineral bone disorder syndrome.

BACKGROUND: The WNT/ß-catenin system is an evolutionarily conserved signaling pathway that plays a crucial role in morphogenesis and cell tissue formation during embryogenesis. Although usually suppressed in adulthood, it can be reactivated during organ damage and regeneration. Transient activation of the WNT/ß-catenin pathway stimulates tissue regeneration after acute kidney injury, while persistent (uncontrolled) activation can promote the development of chronic kidney disease (CKD). CKD-MBD is a clinical syndrome that develops with systemic mineral and bone metabolism disorders caused by CKD, characterized by abnormal bone mineral metabolism and/or extraosseous calcification, as well as cardiovascular disease associated with CKD, including vascular stiffness and calcification. OBJECTIVE: This paper aims to comprehensively review the WNT/ß-catenin signaling pathway in relation to CKD-MBD, focusing on its components, regulatory molecules, and regulatory mechanisms. Additionally, this review highlights the challenges and opportunities for using small molecular compounds to target the WNT/ß-catenin signaling pathway in CKD-MBD therapy. METHODS: We conducted a comprehensive literature review using various scientific databases, including PubMed, Scopus, and Web of Science, to identify relevant articles. We searched for articles that discussed the WNT/ß-catenin signaling pathway, CKD-MBD, and their relationship. We also reviewed articles that discussed the components of the WNT/ß-catenin signaling pathway, its regulatory molecules, and regulatory mechanisms. RESULTS: The WNT/ß-catenin signaling pathway plays a crucial role in CKD-MBD by promoting vascular calcification and bone mineral metabolism disorders. The pathway's components include WNT ligands, Frizzled receptors, and LRP5/6 co-receptors, which initiate downstream signaling cascades leading to the activation of ß-catenin. Several regulatory molecules, including GSK-3ß, APC, and Axin, modulate ß-catenin activation. The WNT/ß-catenin signaling pathway also interacts with other signaling pathways, such as the BMP pathway, to regulate CKD-MBD. CONCLUSIONS: The WNT/ß-catenin signaling pathway is a potential therapeutic target for CKD-MBD. Small molecular compounds that target the components or regulatory molecules of the pathway may provide a promising approach to treat CKD-MBD. However, more research is needed to identify safe and effective compounds and to determine the optimal dosages and treatment regimens.

Chronic kidney disease mineral and bone disorder: A guide for general practice.

BACKGROUND: Chronic kidney disease mineral and bone disorder (CKD-MBD) is an important cause of morbidity, cardiovascular risk and mortality among patients with chronic kidney disease (CKD). The condition begins to manifest in stage 3a CKD. General practitioners play a crucial part in screening, monitoring and early management of this important problem, which is primarily managed in the community. OBJECTIVE: The aim of this article is to summarise the key evidence-based principles of the pathogenesis, assessment and management of CKD-MBD. DISCUSSION: CKD-MBD includes a spectrum of disease involving biochemical changes, bone abnormalities and vascular and soft tissue calcification. Management is centred on monitoring and controlling biochemical parameters with a variety of strategies to improve bone health and cardiovascular risk. The range of evidence-based treatment options is reviewed in this article.

Diagnosis and management of mineral and bone disorders in infants with CKD: clinical practice points from the ESPN CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce.

BACKGROUND: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. METHODS: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2-5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. RESULTS: We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). CONCLUSION: As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. A higher resolution version of the Graphical abstract is available as Supplementary information.

Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease.

SIGNIFICANCE STATEMENT: Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing. Cross-sectionally, acidosis was associated with higher markers of bone remodeling and female-specific impairments in cortical and trabecular bone quality. Prospectively, acidosis was associated with cortical expansion and trabecular microarchitectural deterioration. At the bone-tissue level, acidosis was associated with deficits in bone mineral content. Future work investigating acidosis correction on bone quality is warranted. BACKGROUND: Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineralization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry. METHODS: The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate ≤22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 participants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron microscopy assessed bone biopsy outcomes in 22 participants. RESULTS: The mean age was 68±10 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants. CONCLUSIONS: MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.

Current Status of Mineral and Bone Disorders in Transplant Recipients.

Most patients with end-stage kidney disease undergoing kidney transplantation are affected by the chronic kidney disease-mineral and bone disorder. This entity encompasses laboratory abnormalities, calcification of soft tissues, and the bone abnormalities of renal osteodystrophy that together result in an increased risk of fracture, cardiovascular events, and mortality. Although many biochemical disturbances associated with end-stage kidney disease improve in the first year after transplantation, hyperparathyroidism commonly persists, and residual changes of renal osteodystrophy are slow to resolve. When superimposed on common, traditional risk factors, post-transplant glucocorticoid treatment, the possibility of tubular disturbances and post-transplant chronic kidney disease, rates of incident fracture remain high. This review examines hormonal and biochemical changes before and after kidney transplantation, fracture risk assessment tools and imaging modalities, a staged approach to management and concerns associated with antiresorptive and anabolic therapies. A multidisciplinary approach is proposed as the best means to improve patient-level outcomes.

Inositol 1,4,5-trisphosphate receptor type 2 is associated with the bone-vessel axis in chronic kidney disease-mineral bone disorder.

Objective: The pathogenesis of renal osteopathy and cardiovascular disease suggests the disordered bone-vessel axis in chronic kidney disease-mineral bone disorder (CKD-MBD). However, the mechanism of the bone-vessel axis in CKD-MBD remains unclear.Methods: We established a CKD-MBD rat model to observe the pathophysiological phenotype of the bone-vessel axis and performed RNA sequencing of aortas to identify novel targets of the bone-vessel axis in CKD-MBD.Results: The microarchitecture of the femoral trabecular bone deteriorated and alveolar bone loss was aggravated in CKD-MBD rats. The intact parathyroid hormone and alkaline phosphatase levels increased, 1,25-dihydroxyvitamin D3 levels decreased, and intact fibroblast growth factor-23 levels did not increase in CKD-MBD rats at 16 weeks; other bone metabolic parameters in the serum demonstrated dynamic characteristics. With calcium deposition in the abdominal aortas of CKD-MBD rats, RNA sequencing of the aortas revealed a significant decrease in inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene levels in CKD-MBD rats. A similar trend was observed in rat aortic smooth muscle cells. As a secretory protein, ITPR2 serum levels decreased at 4 weeks and slightly increased without statistical differences at 16 weeks in CKD-MBD rats. ITPR2 serum levels were significantly increased in patients with vascular calcification, negatively correlated with blood urea nitrogen levels, and positively correlated with serum tartrate-resistant acid phosphatase 5b levels.Conclusion: These findings provide preliminary insights into the role of ITPR2 in the bone-vessel axis in CKD-MBD. Thus, ITPR2 may be a potential target of the bone-vessel axis in CKD-MBD.

CKD-MBD biomarkers and CKD progression: an analysis by the joint model.

BACKGROUND: Biomarkers of chronic kidney disease-mineral and bone disorder (CKD-MBD) have been implicated in CKD progression in follow-up studies focusing on single measurements of individual biomarkers made at baseline only. The simultaneous relationship between the time trend of these biomarkers over the course of CKD and renal outcomes has never been tested. METHODS: We applied the joint model (JM) to investigate the longitudinal relationship between repeated measurements of CKD-MBD biomarkers and a combined renal endpoint (estimated glomerular filtration rate reduction >30%, dialysis or transplantation) in 729 stage 2-5 CKD patients over a 36-month follow-up. RESULTS: In the survival submodel of the JM, the longitudinal series of parathyroid hormone (PTH) values was directly and independently related to the risk of renal events [hazard ratio (HR) (1 ln increase in parathyroid hormone (PTH) 2.0 (range 1.5-2.8), P < .001)] and this was also true for repeated measurements of serum phosphate [HR (1 mg/dl) 1.3924 (range 1.1459-1.6918), P = .001], serum calcium [HR (1 mg/dl) 0.7487 (range 0.5843-0.9593), P = .022], baseline fibroblast growth factor 23 [HR (1 pg/ml) 1.001 (range 1.00-1.002), P = .045] and 1,25-dihydroxyvitamin D [HR (1 pg/ml) 0.9796 (range 0.9652-0.9942), P = .006]. CONCLUSION: Repeated measurements of serum PTH, calcium and phosphate as well as baseline FGF23 and 1,25-dihydroxyvitamin D are independently related with the progression to kidney failure in a cohort of stage 2-5 CKD patients. This longitudinal study generates the hypothesis that interventions at multiple levels on MBD biomarkers can mitigate renal function loss in this population.

Investigation on maintenance hemodialysis patients with mineral and bone disorder in Anhui province, China.

BACKGROUND: Chronic kidney disease-mineral bone disorder (CKD-MBD) is a common comorbidity in patients with CKD. The study aims to describe the control rates of serum-corrected calcium (Ca), phosphate (P) and intact parathyroid hormone (iPTH) and its risk factors among maintenance hemodialysis (MHD) patients in Anhui Province of China. METHODS: The study was conducted in 27 hemodialysis centers of Anhui Province between January 1st 2020 and December 31th 2020. Chi-square test was used to compare the control rates of serum-corrected Ca, P and iPTH between the present study and DOPPS 4 or Anhui Province in 2014. Binary logistic regression analysis was used to explore the risk factors of the control rates of serum-corrected Ca, P and iPTH. RESULTS: A total of 3 025 MHD patients were recruited in this study, with a mean age of 54.8 (SD: 12.8) years, and 60.1% were males. According to the Chinese Diagnosis and Treatment Guidelines for CKD-MBD, the control rates of serum-corrected Ca, P and iPTH in the present study were 57.9%, 20.0% and 56.0%, respectively. Based on KDOQI guidelines (2003), the control rates of the above indicators were 43.1%, 35.3% and 22.3%, respectively. The control rates of serum-corrected Ca, P and iPTH in this study were lower than those of DOPPS 4 (P < 0.001). Compared to the results of Anhui Province in 2014, the control rate of corrected Ca was higher (P < 0.001) and the control rate of iPTH was lower (P = 0.005). Age, residential area, BMI, dialysis vintage, albumin and hemoglobin levels were factors of serum-corrected Ca, P and iPTH not within target range. CONCLUSION: The control rates of serum-corrected Ca, P and iPTH in MHD patients in Anhui Province are relatively low. Monitoring and management should be strengthened to improve the prognosis of patients undergoing dialysis.

[Diagnosis and treatment of osteoporosis in patients with chronic kidney disease : Joint guidelines of the Austrian Society for Bone and Mineral Research (ÖGKM), the Austrian Society of Physical and Rehabilitation Medicine (ÖGPMR) and the Austrian Society of Nephrology (ÖGN)]. / Diagnose und Therapie der Osteoporose bei Patienten mit chronischer Niereninsuffizienz : Gemeinsame Leitlinie der Österreichischen Gesellschaft für Knochen- und Mineralstoffwechsel (ÖGKM), der Österreichischen Gesellschaft für Physikalische Medizin und Rehabilitation (ÖGPMR) und der Österreichischen Gesellschaft für Nephrologie (ÖGN).

DEFINITION AND EPIDEMIOLOGY: Chronic kidney disease (CKD): abnormalities of kidney structure or function, present for over 3 months. Staging of CKD is based on GFR and albuminuria (not graded). Osteoporosis: compromised bone strength (low bone mass, disturbance of microarchitecture) predisposing to fracture. By definition, osteoporosis is diagnosed if the bone mineral density T­score is ≤ -2.5. Furthermore, osteoporosis is diagnosed if a low-trauma (inadequate trauma) fracture occurs, irrespective of the measured T­score (not graded). The prevalence of osteoporosis, osteoporotic fractures and CKD is increasing worldwide (not graded). PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD): Definition of CKD-MBD: a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; renal osteodystrophy; vascular calcification (not graded). Increased, normal or decreased bone turnover can be found in renal osteodystrophy (not graded). Depending on CKD stage, routine monitoring of calcium, phosphorus, alkaline phosphatase, PTH and 25-OH-vitamin D is recommended (2C). Recommendations for treatment of CKD-MBD: Avoid hypercalcemia (1C). In cases of hyperphosphatemia, lower phosphorus towards normal range (2C). Keep PTH within or slightly above normal range (2D). Vitamin D deficiency should be avoided and treated when diagnosed (1C). DIAGNOSIS AND RISK STRATIFICATION OF OSTEOPOROSIS IN CKD: Densitometry (using dual X­ray absorptiometry, DXA): low T­score correlates with increased fracture risk across all stages of CKD (not graded). A decrease of the T­score by 1 unit approximately doubles the risk for osteoporotic fracture (not graded). A T-score ≥ -2.5 does not exclude osteoporosis (not graded). Bone mineral density of the lumbar spine measured by DXA can be increased and therefore should not be used for the diagnosis or monitoring of osteoporosis in the presence of aortic calcification, osteophytes or vertebral fracture (not graded). FRAX can be used to aid fracture risk estimation in all stages of CKD (1C). Bone turnover markers can be measured in individual cases to monitor treatment (2D). Bone biopsy may be considered in individual cases, especially in patients with CKD G5 (eGFR < 15 ml/min/1.73 m2) or CKD 5D (dialysis). SPECIFIC TREATMENT OF OSTEOPOROSIS IN PATIENTS WITH CKD: Hypocalcemia should be treated and serum calcium normalized before initiating osteoporosis therapy (1C). CKD G1-G2 (eGFR ≥ 60 ml/min/1.73 m2): treat osteoporosis as recommended for the general population (1A). CKD G3-G5D (eGFR < 60 ml/min/1.73 m2 to dialysis): treat CKD-MBD first before initiating osteoporosis treatment (2C). CKD G3 (eGFR 30-59 ml/min/1.73 m2) with PTH within normal limits and osteoporotic fracture and/or high fracture risk according to FRAX: treat osteoporosis as recommended for the general population (2B). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) with osteoporotic fracture (secondary prevention): Individualized treatment of osteoporosis is recommended (2C). CKD G4-5 (eGFR < 30 ml/min/1.73 m2) and high fracture risk (e.g. FRAX score > 20% for a major osteoporotic fracture or > 5% for hip fracture) but without prevalent osteoporotic fracture (primary prevention): treatment of osteoporosis may be considered and initiated individually (2D). CKD G4-5D (eGFR < 30 ml/min/1.73 m2 to dialysis): Calcium should be measured 1-2 weeks after initiation of antiresorptive therapy (1C). PHYSICAL MEDICINE AND REHABILITATION: Resistance training prioritizing major muscle groups thrice weekly (1B). Aerobic exercise training for 40 min four times per week (1B). Coordination and balance exercises thrice weekly (1B). Flexibility exercise 3-7 times per week (1B).

Osteomalacia and Renal Osteodystrophy.

Osteomalacia is defined by the undermineralization of newly formed bone due to a lack of available calcium, phosphorus, or vitamin D. Causative factors of osteomalacia include nutritional deficiency, diminished absorptive capabilities (often due to gastrointestinal disorders), and renal insufficiency. Renal osteodystrophy is a specific form of metabolic bone disease defined by the presence of osteomalacia and associated hyperparathyroidism secondary to a malfunction in, or absence of, renal parenchyma. This reduces the conversion of vitamin D to its active form, thus leading to a cascade of effects that negatively impact the stability of the skeleton. Osteomalacia occurs across a spectrum of severity and can produce severe consequences for specific populations, including patients with dietary, nutritional, and absorptive deficiencies. Renal osteodystrophy affects patients with chronic kidney disease, those undergoing dialysis, and renal transplant patients. Special considerations must be taken into account when assessing the bone health of patients fitting these criteria.

Adynamic bone disease: Revisited.

The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.